Inhalation of cadmium, a known environmental pollutant and a contaminant of cigarette smoke, induces the synthesis of a metallothionein - like protein in the lungs of rodents. The purpose of our research project is to study the synthesis and role of this pulmonary protein in the rat. First we will determine the relationship between cadmium inhalation conditions (i.e., concentration, frequency of exposure, and solubility of Cd compound) and cadmium and metallothionein levels in the lung, kidney, and liver. Then, by means of bronchopulmonary lavage, elutriator centrifugation, and density gradient techniques, we will isolate alveolar macrophages, Type II alveolar cells, and Clara cells from cadmium exposed animals and quantitate cellular levels of metallothionein with a radio-immune assay. To test the hypothesis that pulmonary metallothionein plays a protective role in the lung we will determine whether: 1) multiple Cd exposures lead to the development of pulmonary tolerance to Cd; and 2) pre-treatment of rats with low dose Cd concentrations (a) offers pulmonary protection against a subsequent challenge with a highly toxic dose or (b) increases the ability of the lungs to retain Cd and, as a consequence, spares the kidneys and liver. Cd-induced lung damage will be assessed cytologically by determining the number and type of free alveolar cells, biochemically by assaying for cellular enzymes in lavage fluid, and histologically. To test the hypothesis that metallothionein when present extracellularly has a deleterious effect on pulmonary tissue and cells, we will determine whether: 1) intratracheal instillation of metallothionein has greater cytotoxic effects on the lung than an equivalent amount of cadmium as CdC12 and 2) the viability and/or growth of lung cells (i.e., lung fibroblasts, alveolar macrophages, Type II cells) is more affected by the presence of metallothionein than by an equivalent amount of Cd.